1. Field of the Invention
This invention relates to uncoated direct compression tablets containing cefadroxil monohydrate as the active ingredient, which are capable of oral administration to human beings by swallowing, chewing or disintegrating in water resulting in a drinkable dispersion.
2. Background Art
Solid dosage forms, such as tablets and capsules, have been used for many years for orally administering a medicine to a human being.
A problem occurring is the need to protect certain active substances against loss of substance, of potency and/or physico-chemical characteristics due to contact with the atmosphere, recrystallization and/or sublimation. For this purpose, several devices have been constructed, such as sugar-coated, film-coated and compression-coated tablets, capsules and micro-capsules. The latter are quite expensive to produce and also tend to decreased bioavailability, while the other forms of protection hitherto devised, almost by definition, were to be considered incompatible with the principle of the dispersible tablet, i.e. the ability to rapidly disintegrate in water.
Examples of tablets having a core containing active material with a coated outer surface are U.S. Pat. No. 5,366,738 to Rork, et al; U.S. Pat. No. 5,284,662 to Koparkar, et al; U.S. Pat. No. 5,256,440 to Appel, et al; U.S. Pat. No. 5,213,808 to Bar-Shalom et al; U.S. Pat. No. 5,047,246 to Gallian, et al; and U.S. Pat. No. 4,414,204 to Tarcsay, et al.
Additionally, patents relating to controlled-release tablet formulations are U.S. Pat. No. 4,968,508 to Oren, et al; and U.S. Pat. No. 4,851,228 to Zentner, et al.
U.S. Pat. No. 4,910,023 to Botzolakis, et al discloses a tablet containing a drug active in combination with a flavor masking agent.
Besides the solid dosage forms such as tablets, there is also an increasing demand for liquid, drinkable preparations. This is especially the case with the elderly and with children, and the more so when large doses of the medicament are to be taken frequently and/or for extended periods.
Drinkable preparations can sometimes be delivered to the patient already in their liquid form, in solution, suspension or emulsion. This always has obvious logistic disadvantages, and moreover many medicaments tend then to decompose quite quickly.
A good alternative is to supply the medicament in a special solid formulation, which on putting into water will quickly disintegrate to form a mixture which is homogeneous and agreeable enough to be drinkable. Examples are effervescent tablets and dispersion tablets, the former depending on the reaction of bicarbonate or carbonate with an acid or on other excipients having the capacity of developing gas after contact with water, the latter on the presence of disintegrating agents having the capacity to swell with water. While many medicaments are incompatible with bicarbonate and/or with acids, the dispersion tablets are the more generally suitable of the two sorts.
Examples of such tablet formulations which are dispersible in water are reported in European Application 181,650B1 published on Aug. 29, 1990 and WO 96/24337 published on Aug. 15, 1996.
Although such water-dispersible tablet formulations have been reported in the literature, such tablets have several deficiencies. They can involve using specially adapted equipment, which is not standard or readily available as in application 181,650, as well as expensive time-consuming procedures for applying an outer protective coating.
Also, it would additionally be highly desirable to provide a tablet formulation that is not only capable of being swallowed or dispersed quickly in water to form a drinkable dispersion, but also is capable of being chewed and rapidly disintegrates in the mouth so that it has a pleasant taste and can be easily swallowed. This is particularly important for those people having trouble swallowing a tablet that is still intact, but yet do not have immediate access to water to disperse the same therein to form a drinkable dispersion.
Cefadroxil monohydrate is a widely used broad spectrum cephalosporin antibiotic that can be administered orally in adults and children. It is sold worldwide by Bristol-Myers Squibb Company under various trade names, including Duricef.RTM. and Duracef.RTM. in the form of gelatin capsules, uncoated tablets and powder for reconstitution with water to form a liquid suspension, and is dosed several times daily depending on the type of bacterial infection and the patient's needs (i.e. adult, elderly or pediatric).
Therefore, to fulfill the various diverse needs of the patient being treated, and to overcome the aforementioned disadvantages of prior art tablet formulations, it would be highly desirable to provide a tablet of cefadroxil monohydrate that is uncoated (for ease of preparation) and is chewable, swallowable and easily dispersible in water to form a pleasant tasting drinkable dispersion for oral administration to a human being.
It has now surprisingly been found possible to provide such a tablet formulation for cefadroxil monohydrate possessing the aforementioned attributes.